Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood

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  • Yan Zheng, Key Laboratory of Public Health Safety of Ministry of Education, School of Public Health, Fudan University, Shanghai, China. yan_zheng@fudan.edu.cn., Kina
  • Tao Huang, Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China., Kina
  • Tiange Wang, Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal St, Suite 1724, New Orleans, LA, 70112, USA.
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  • Zhendong Mei, Department of Cardiology Zhongshan Hospital, State Key Laboratory of Genetic Engineering School of Life Sciences, Human Phenome Institue, Fudan University, 2005 Songhu Road, Shanghai, 200438, China.
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  • Zhonghan Sun, Department of Cardiology Zhongshan Hospital, State Key Laboratory of Genetic Engineering School of Life Sciences, Human Phenome Institue, Fudan University, 2005 Songhu Road, Shanghai, 200438, China.
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  • Tao Zhang, Department of Biostatistics, School of Public Health, Shandong University, Jinan, 250012, China.
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  • Christina Ellervik, Division of Genetics, Boston Children's Hospital, Boston, MA, USA; Division of Developmental Medicine, Boston Children's Hospital, Boston, MA, USA.
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  • Jin-Fang Chai, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, 117549, Singapore.
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  • Xueling Sim, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, 117549, Singapore.
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  • Rob M van Dam, Saw Swee Hock School of Public Health, National University of Singapore, Singapore, 117549, Singapore.
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  • E-Shyong Tai, Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore.
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  • Woon-Puay Koh, Health Services and Systems Research, Duke-NUS (National University of Singapore) Medical School, Singapore.
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  • Rajkumar Dorajoo, Division of Human Genetics, Genome Institute of Singapore, Agency for Science, Technology and Research (A*STAR), Singapore.
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  • Seang-Mei Saw, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
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  • Charumathi Sabanayagam, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
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  • Tien Yin Wong, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
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  • Preeti Gupta, Singapore Eye Research Institute, Singapore National Eye Centre, Singapore.
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  • Peter Rossing, Københavns Universitet
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  • Tarunveer S Ahluwalia, COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark.
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  • Rebecca K Vinding, COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark., Danmark
  • Hans Bisgaard, COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark., Danmark
  • Klaus Bønnelykke, COPSAC, Copenhagen Prospective Studies on Asthma in Childhood, Herlev and Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark., Danmark
  • Yujie Wang, Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
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  • Mariaelisa Graff, Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27514, USA.
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  • Trudy Voortman, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands ; Department of Internal Medicine, Genetics Laboratory, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
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  • Frank J A van Rooij, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands ; Department of Internal Medicine, Genetics Laboratory, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
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  • Albert Hofman, Department of Epidemiology, Harvard School of Public Health, Harvard University, Boston, MA, USA; Department of Nutrition, Harvard School of Public Health, Boston, MA, USA.
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  • Diana van Heemst, Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
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  • Raymond Noordam, Section of Gerontology and Geriatrics, Department of Internal Medicine, Leiden University Medical Center, Leiden, The Netherlands.
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  • Angela C Estampador, Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Lund University, 21741, Malmö, Sweden.
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  • Tibor V Varga, Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Skåne University Hospital Malmö, Lund University, 21741, Malmö, Sweden.
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  • Cornelia Enzenbach, Institute for Laboratory Medicine, University of Leipzig, Leipzig, Germany.
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  • Markus Scholz, LIFE Research Center for Civilisation Diseases, University of Leipzig, Leipzig, Germany.
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  • Joachim Thiery, LIFE Research Center for Civilisation Diseases, University of Leipzig, Leipzig, Germany.
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  • Ralph Burkhardt, Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Regensburg, Regensburg, Germany.
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  • Marju Orho-Melander, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
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  • Christina-Alexandra Schulz, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
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  • Ulrika Ericson, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
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  • Emily Sonestedt, Department of Clinical Sciences Malmö, Lund University, Malmö, Sweden.
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  • Michiaki Kubo, Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama City, Japan.
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  • Masato Akiyama, Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama City, Japan.
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  • Ang Zhou, South Australian Academic Health Science and Translation Centre, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia.
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  • Tuomas O Kilpeläinen, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200N, Copenhagen, Denmark.
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  • Torben Hansen, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200N, Copenhagen, Denmark., Danmark
  • Marcus E Kleber, Competence Cluster of Nutrition and Cardiovascular Health (nutriCARD) Halle-Jena-Leipzig, Copenhagen, Germany.
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  • Graciela Delgado, Vth Department of Medicine, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany.
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  • Mark McCarthy, Oxford Centre for Diabetes, Endocrinology and Metabolism, Churchill Hospital, University of Oxford, Old Road, Headington, Oxford, OX3 7LJ, UK.
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  • Rozenn N Lemaitre, Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, 98101, USA.
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  • Janine F Felix, Department of Pediatrics, Division of Respiratory Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
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  • Vincent W V Jaddoe, Department of Pediatrics, Division of Respiratory Medicine, Erasmus MC-University Medical Center Rotterdam, Rotterdam, The Netherlands.
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  • Ying Wu, Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA.
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  • Karen L Mohlke, Department of Genetics, University of North Carolina, Chapel Hill, North Carolina 27599-7264, USA.
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  • Terho Lehtimäki, Department of Clinical Chemistry, University of Tampere School of Medicine, 33014, Tampere, Finland.
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  • Carol A Wang, School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Callaghan, NSW, 2308, Australia.
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  • Craig E Pennell, School of Medicine and Public Health, Faculty of Medicine and Health, The University of Newcastle, Callaghan, NSW, 2308, Australia.
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  • Heribert Schunkert, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
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  • Thorsten Kessler, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
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  • Lingyao Zeng, Deutsches Herzzentrum München, Technische Universität München, Munich, Germany.
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  • Christina Willenborg, Department of Clinical Chemistry, University of Tampere School of Medicine, 33014, Tampere, Finland.
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  • Annette Peters, Institute of Epidemiology and PopGen Biobank, Kiel University, Kiel, Germany.
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  • Wolfgang Lieb, Institute of Epidemiology and PopGen Biobank, Kiel University, Kiel, Germany.
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  • Veit Grote, Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, Klinikum der Universitaet Muenchen, Munich, Germany.
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  • Peter Rzehak, Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, Klinikum der Universitaet Muenchen, Munich, Germany.
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  • Berthold Koletzko, Division of Metabolic and Nutritional Medicine, Dr von Hauner Children's Hospital, Klinikum der Universitaet Muenchen, Munich, Germany.
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  • Jeanette Erdmann, Institute for Cardiogenetics, University of Lübeck, 23562, Lübeck, Germany.
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  • Matthias Munz, Charité - University Medicine Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Institute for Dental and Craniofacial Sciences, Department of Periodontology and Synoptic Dentistry, 14197 Berlin, Germany.
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  • Tangchun Wu, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, Hubei, China.
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  • Meian He, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, Hubei, China.
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  • Caizheng Yu, MOE Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, 430030, Hubei, China.
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  • Cécile Lecoeur, University of Lille, CNRS, Institut Pasteur of Lille, Lille, France.
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  • Philippe Froguel, University of Lille, CNRS, Institut Pasteur of Lille, Lille, France.
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  • Dolores Corella, CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, Spain.
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  • Luis A Moreno, Growth Exercise, Nutrition and Development (GENUD) Research Group, Facultad de Ciencias de La Salud, Universidad de Zaragoza, Zaragoza, Spain.
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  • Chao-Qiang Lai, USDA ARS, Human Nutrition Research Center on Aging at Tufts University, Boston, MA, 02111, USA.
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  • Niina Pitkänen, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, 20520, Turku, Finland.
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  • Colin A Boreham, UCD Institute for Sport & Health, University College Dublin, Dublin, Ireland.
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  • Paul M Ridker, Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02215, USA.
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  • Frits R Rosendaal, Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, Leiden, the Netherlands.
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  • Renée de Mutsert, Department of Clinical Epidemiology, Leiden University Medical Center, University of Leiden, Leiden, the Netherlands.
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  • Chris Power, Population, Policy and Practice Programme, UCL Institute of Child Health, London, UK.
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  • Lavinia Paternoster, MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, BS82BN, UK.
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  • Thorkild I A Sørensen, Vth Department of Medicine, Mannheim Medical Faculty, Heidelberg University, Mannheim, Germany., MRC Integrative Epidemiology Unit, Bristol Medical School, University of Bristol, Bristol, BS82BN, UK., Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, 1353K, Copenhagen, Denmark.
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  • Anne Tjønneland, Danish Cancer Society Research Center, Danish Cancer Society, Strandboulevarden 49, 2100, Copenhagen Ø, Denmark. skriver@cancer.dk., Danmark
  • Kim Overvad
  • Luc Djousse, Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass., USA.
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  • Fernando Rivadeneira, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands ; Department of Internal Medicine, Genetics Laboratory, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands.
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  • Nanette R Lee, Department of Anthropology, Sociology, and History, University of San Carlos, 6000, Cebu City, Philippines.
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  • Olli T Raitakari, Centre for Population Health Research, University of Turku and Turku University Hospital, Turku, Finland.
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  • Mika Kähönen, Department of Clinical Physiology, Faculty of Medicine and Health Technology, Tampere University, 33014, Tampere, Finland.
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  • Jorma Viikari, Department of Medicine, University of Turku, 20520, Turku, Finland.
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  • Jean-Paul Langhendries, Department of Paediatrics and NICU, CHC-Site St-Vincent, Liège-Rocourt, Belgium.
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  • Joaquin Escribano, Paediatrics Research Unit, Universitat Rovira I Virgili, IISPV, Reus, Spain.
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  • Elvira Verduci, Department of Pediatrics, San Paolo Hospital, University of Milan, Milan, Italy.
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  • George Dedoussis, Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.
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  • Inke König, Institut für Medizinische Biometrie Und Statistik, Universität Zu Lübeck, Lübeck, Germany.
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  • Beverley Balkau, Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, The Netherlands; Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Environmental Epidemiology of Cancer Team, F-94807, Villejuif, France; Univ Paris Sud, UMRS 1018, F-94805, Villejuif, France.
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  • Oscar Coltell, Department of Computer Languages and Systems, University Jaume I, 12071, Castellon, Spain.
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  • Jean Dallongeville, INSERM U1167, Institut Pasteur de Lille, Univ. Lille, Lille, France.
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  • Aline Meirhaeghe, INSERM U1167, Institut Pasteur de Lille, Univ. Lille, Lille, France.
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  • Philippe Amouyel, INSERM U1167, Institut Pasteur de Lille, Univ. Lille, Lille, France.
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  • Frédéric Gottrand, INSERM U1286, Hôpital Jeanne de Flandre, CHU Lille, Univ. Lille, Lille, France.
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  • Katja Pahkala, Department of Physical Activity and Health, Paavo Nurmi Centre, Sports and Exercise Medicine Unit, Turku, Finland.
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  • Harri Niinikoski, Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, 20521, Turku, Finland.
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  • Elina Hyppönen, South Australian Academic Health Science and Translation Centre, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, SA, Australia.
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  • Winfried März, Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Graz, Austria.
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  • David A Mackey, Centre For Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Crawley, Australia.
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  • Dariusz Gruszfeld, Department of Neonatology and Neonatal Intensive Care, The Children's Memorial Health Institute, Al. Dzieci Polskich 20, 04-730, Warsaw, Poland.
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  • Katherine L Tucker, Biomedical and Nutritional Sciences, University of Massachusetts Lowell, Lowell, MA, USA.
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  • Frédéric Fumeron, Sorbonne Universités, UPMC Univ Paris 06, UMR_S 1138, Centre de Recherche Des Cordeliers, 75006, Paris, France.
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  • Ramon Estruch, Department of Internal Medicine, Hospital Clinic, IDIBAPS, 08036, Barcelona, Spain.
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  • Jose M Ordovas, IMDEA Food Institute, CEI UAM + CSIC, Madrid, Spain.
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  • Donna K Arnett, College of Public Health, University of Kentucky, Lexington, KY, UK.
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  • Dennis O Mook-Kanamori, Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, The Netherlands.
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  • Dariush Mozaffarian, Friedman School of Nutrition Science & Policy, Tufts University, Boston, MA, 02111, USA.
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  • Bruce M Psaty, Kaiser Permanent Washington Health Research Institute, Seattle, WA, USA.
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  • Kari E North, Carolina Center for Genome Sciences, University of North Carolina, Chapel Hill, NC, 27514, USA.
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  • Daniel I Chasman, Department of Medicine, Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, Mass., USA.
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  • Lu Qi, Department of Epidemiology, School of Public Health and Tropical Medicine, Tulane University, 1440 Canal St, Suite 1724, New Orleans, LA, 70112, USA. lqi1@tulane.edu.

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (β = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (β = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (β = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.

OriginalsprogEngelsk
TidsskriftEuropean Journal of Epidemiology
Vol/bind35
Nummer7
Sider (fra-til)685-697
Antal sider13
ISSN0393-2990
DOI
StatusUdgivet - jul. 2020

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